Microscopic foundation of multimodal human imaging

人脑的计算特性源于数十亿个神经元之间复杂的相互作用 在复杂的网络中相互连接。然而，我们在健康人脑中研究这些网络的能力是有限的。 使用非侵入性技术的必要性。这与动物模型形成了鲜明对比，在动物模型中 由于显微光学的最新进展，对细胞水平的大脑功能的观察已经成为可能 成像和遗传学。因此，当今神经科学面临的一个核心挑战是如何利用这些机械原理 来自动物研究的见解，以准确地从人类非侵入性信号中得出生理推断。 在提议的项目中，我们将重点放在“校准的”血氧水平依赖(BOLD)功能磁共振成像 科技提出了这样的问题：“可以可靠地推断出潜在神经元活动的哪些方面 从无创脑血流量(CBF)和脑O2代谢率(CMRO2)观察？和 “结合校准的BOLD和脑磁图可以获得哪些进一步的信息？ (梅格)？“ 我们的中心假设是，特定的神经细胞类型在他们驾驶的方式上有可识别的“信号” 能量代谢(CMRO2)、血流(CBF)的变化并有助于宏观电信号 (MEG电流偶极子动力学)。由于其他因素可能会影响基线流量和新陈代谢，我们的重点是 根据诱发的绝对CMRO2和CBF的变化与神经元活动的增加或减少相关。 我们将在老鼠和人类身上进行平行实验，从经验上将 脑功能组织的微观特征及其在宏观层面上的表现 非侵入性的观察物。基于实验结果，我们将开发一个计算框架 这将在规模和测量模式之间建立联系，从而能够稳健地估计 人体神经回路活动的非侵入性测量的关键方面。 拟议中的项目将为人类大脑中已知细胞类型的神经元活动提供一个定量探针。 实现人类功能磁共振研究的范式转变：从简单的功能磁共振信号变化映射到显式映射 在没有混淆效应的情况下估计特定神经细胞类型的各自的活动水平 流动和新陈代谢的基线状态。

The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use noninvasive technologies. This is in contrast to animal models where a rich, detailed view on the cellular level brain function has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from human noninvasive signals. In the proposed project, we focus on the “Calibrated” Blood Oxygenation Level Dependent (BOLD) fMRI technology asking the questions: “Which aspects of the underlying neuronal activity can be reliably inferred from noninvasive cerebral blood flow (CBF) and Cerebral Metabolic Rate of O2 (CMRO2) observables?” and “What further information can be obtained from combining Calibrated BOLD with Magnetoencephalography (MEG)?” Our central hypothesis is that specific neuronal cell types have identifiable “signatures” in the way they drive changes in energy metabolism (CMRO2), blood flow (CBF) and contribute to macroscopic electrical signals (MEG current dipole dynamics). Because other factors may affect baseline flow and metabolism, our focus is on the evoked absolute CMRO2 and CBF changes associated with increased or decreased neuronal activity. We will perform parallel experiments in mice and humans to empirically connect the dots between the microscopic properties of brain's functional organization and their manifestation on the macroscopic level of noninvasive observables. Based on the experimental results, we will then develop a computational framework that will establish connections between scales and measurement modalities enabling robust estimation of the critical aspects of neuronal circuit activity from noninvasive measurements in humans. The proposed project will deliver a quantitative probe for neuronal activity of known cell types in human brain enabling a paradigm shift in human fMRI studies: from a simple mapping of fMRI signal change to the explicit estimation of the respective activity levels of specific neuronal cell types without confounding effects of the baseline state of flow and metabolism.